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Abstract

Susceptibility to PTSD is determined by both genes and environment. Similarly, gene-expression levels in peripheral blood are influenced by both genes and environment, and expression levels of many genes show good correspondence between peripheral blood and brain. Therefore, our objectives were to test the following hypotheses: (1) pre-trauma expression levels of a gene subset (particularly immune-system genes) in peripheral blood would differ between trauma-exposed Marines who later developed PTSD and those who did not; (2) a predictive biomarker panel of the eventual emergence of PTSD among high-risk individuals could be developed based on gene expression in readily assessable peripheral blood cells; and (3) a predictive panel based on expression of individual exons would surpass the accuracy of a model based on expression of full-length gene transcripts. Gene-expression levels were assayed in peripheral blood samples from 50 U.S. Marines (25 eventual PTSD cases and 25 non-PTSD comparison subjects) prior to their deployment overseas to war-zones in Iraq or Afghanistan. The panel of biomarkers dysregulated in peripheral blood cells of eventual PTSD cases prior to deployment was significantly enriched for immune genes, achieved 70% prediction accuracy in an independent sample based on the expression of 23 full-length transcripts, and attained 80% accuracy in an independent sample based on the expression of one exon from each of five genes. If the observed profiles of pre-deployment mRNA-expression in eventual PTSD cases can be further refined and replicated, they could suggest avenues for early intervention and prevention among individuals at high risk for trauma exposure.